Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

Luis M. García-Marín, Adrian I. Campos, Santiago Diaz-Torres, Jill A. Rabinowitz, Zuriel Ceja, Brittany L. Mitchell, Katrina L. Grasby, Jackson G. Thorp, Ingrid Agartz, Saud Alhusaini, David Ames, Philippe Amouyel, Ole A. Andreassen, Konstantinos Arfanakis, Alejandro Arias-Vasquez, Nicola J. Armstrong, Lavinia Athanasiu, Mark E. Bastin, Alexa S. Beiser, David A. BennettJoshua C. Bis, Marco P.M. Boks, Dorret I. Boomsma, Henry Brodaty, Rachel M. Brouwer, Jan K. Buitelaar, Ralph Burkhardt, Wiepke Cahn, Vince D. Calhoun, Owen T. Carmichael, Mallar Chakravarty, Qiang Chen, Christopher R.K. Ching, Sven Cichon, Benedicto Crespo-Facorro, Fabrice Crivello, Anders M. Dale, George Davey Smith, Eco J.C. de Geus, Philip L. De Jager, Greig I. de Zubicaray, Stéphanie Debette, Charles DeCarli, Nynke A. Groenewold, Pieter J. Hoekstra, Wiro J. Niessen, Brenda W.J.H. Penninx, Lianne Schmaal, Dennis van der Meer, Sarah E Medland, Miguel E Rentería*

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

Samenvatting

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson’s disease and attention-deficit/hyperactivity disorder. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases.

Originele taal-2English
Pagina's (van-tot)2333-2344
Aantal pagina's12
TijdschriftNature genetics
Volume56
Nummer van het tijdschrift11
DOI's
StatusPublished - nov.-2024

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